Mechanical coupling in myosin V: A simulation study Export

@article{citeulike:6002512, abstract = {Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The inter-domain coupling in myosin V is studied with Restrained Targeted Molecular Dynamics (RTMD) using an all-atom representation in explicit solvent. To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FS) in the direction of their displacement from the rigor conformation, which has a closed actin-binding cleft, to the post-rigor conformation, in which the cleft is open. The 'minimal' FS that results in extensive structural changes in the overall myosin conformation is comprised of the ATP, Switch 1, and the nearby HF, HG and HH helices. Addition of switch 2 to the forcing set is required to achieve a complete opening of the actin-binding cleft. The RTMD simulations reveal the mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin-binding cleft and the converter. Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft, and leads to the rupture of a key hydrogen bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft may mediate the rupture of this bond via a connection between the HW helix, the Relay helix, and Switch 2. The findings are consistent with experimental studies and a recent normal mode analysis. The present method is expected to be useful more generally in studies of inter-domain coupling in proteins.}, author = {Ovchinnikov, Victor and Trout, Bernhardt L. and Karplus, Martin}, citeulike-article-id = {6002512}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jmb.2009.10.029}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0022283609012698}, day = {21}, doi = {10.1016/j.jmb.2009.10.029}, issn = {00222836}, journal = {Journal of Molecular Biology}, keywords = {myosin, smd}, month = {October}, posted-at = {2009-10-30 00:21:59}, priority = {2}, title = {Mechanical coupling in myosin V: A simulation study}, url = {http://dx.doi.org/10.1016/j.jmb.2009.10.029}, year = {2009} }

TY - JOUR ID - citeulike:6002512 L3 - citeulike-article-id:6002512 N2 - Myosin motor function depends on the interaction between different domains that transmit information from one part of the molecule to another. The inter-domain coupling in myosin V is studied with Restrained Targeted Molecular Dynamics (RTMD) using an all-atom representation in explicit solvent. To elucidate the origin of the conformational change due to the binding of ATP, targeting forces are applied to small sets of atoms (the forcing sets, FS) in the direction of their displacement from the rigor conformation, which has a closed actin-binding cleft, to the post-rigor conformation, in which the cleft is open. The ‘minimal’ FS that results in extensive structural changes in the overall myosin conformation is comprised of the ATP, Switch 1, and the nearby HF, HG and HH helices. Addition of switch 2 to the forcing set is required to achieve a complete opening of the actin-binding cleft. The RTMD simulations reveal the mechanical coupling pathways between (i) the nucleotide-binding pocket (NBP) and the actin-binding cleft, (ii) the NBP and the converter, and (iii) the actin-binding cleft and the converter. Closing of the NBP due to ATP binding is tightly coupled to the opening of the cleft, and leads to the rupture of a key hydrogen bond (F441N/A684O) between switch 2 and the SH1 helix. The actin-binding cleft may mediate the rupture of this bond via a connection between the HW helix, the Relay helix, and Switch 2. The findings are consistent with experimental studies and a recent normal mode analysis. The present method is expected to be useful more generally in studies of inter-domain coupling in proteins. JF - Journal of Molecular Biology SN - 00222836 TI - Mechanical coupling in myosin V: A simulation study KW - myosin KW - smd AU - Ovchinnikov, Victor AU - Trout, Bernhardt AU - Karplus, Martin PY - 2009/10/21/ UR - http://dx.doi.org/10.1016/j.jmb.2009.10.029 ER -